Phase II of Zactima Maintenance for Locally Advanced or Metastatic Non-small-cell Lung Carcinoma (NSCLC) Following Platinum-doublet Chemotherapy
Study Details
Study Description
Brief Summary
This study is multicenter, randomized, double-blinded, placebo-controlled Phase II study comparing vandetanib (300mg daily) plus best supportive care (BSC) to placebo plus BSC as maintenance treatment in patients with locally advanced or metastatic NSCLC, who have received and responded to prior platinum-doublet systemic chemotherapy. The primary objective of the study is to compare the Progression Free Survival (PFS) rate at 3 months in locally advanced or metastatic NSCLC patients with or without vandetanib maintenance.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vandetanib
|
Drug: Vandetanib
Tablet, oral, daily
Other Names:
|
| Placebo Comparator: Placebo
|
Drug: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) Rate at 3 Months [12 weeks]
Progression-free survival (PFS) rate at 3 months is defined as the number of patients without evidence of progression or death after 3 months from randomisation among the PFS-evaluable patients.
Secondary Outcome Measures
- Progression-free Survival (PFS) [Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression.]
Progression-free survival (PFS) defined as the median time from randomization to death from any cause or first observed disease progression.
- Overall Survival (OS) [Every 12 weeks unless the patient withdraws consent]
Overall survival (OS) defined as the median time from randomization to death from any cause.
- Disease of Response (DOR) [Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression.]
Number of patients showing Complete Response (CR), Partial Response (PR) or Stable Disease (SD) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions), Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) or Stable Disease (SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum longest diameter since the treatment started) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response
- Objective Response Rate (ORR) [Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression.]
Number of patients showing Complete Response (CR) or Partial Response (PR) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (IIIb-IV) at the time of original diagnosis.
-
Completion of 4 cycles of chemotherapy of gemcitabine (1,000 or 1250mg/m2/day on day 1 and 8) and cisplatin (70-80mg/m2/day on day 1) every 3 weeks and have shown response, Complete Response(CR), Partial Response (PR) or stable disease (SD) by RECIST.
-
WHO PS 0-1
-
No prior radiotherapy to chest, immunotherapy or biologic therapy
Exclusion Criteria:
-
Mixed small cell and non small-cell lung cancer history.
-
Prior treatment with EGFR TKIs or VEGFR TKIs (prior treatment with cetuximab [Erbitux] or bevacizumab [Avastin] is not permitted.)
-
Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol.
-
Radiation therapy within 4 weeks before the start of study therapy. Major surgery within 4 weeks, or incomplete healed surgical incision before starting study therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | CheongJu | Republic of Korea | Korea, Republic of | |
| 2 | Research Site | Gyeonggi-do | Republic of Korea | Korea, Republic of | |
| 3 | Research Site | Gyeongsangnam-Do | Republic of Korea | Korea, Republic of | |
| 4 | Research Site | Incheon | Republic of Korea | Korea, Republic of | |
| 5 | Research Site | Seoul | Republic of Korea | Korea, Republic of |
Sponsors and Collaborators
- Genzyme, a Sanofi Company
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D4200C00077
Study Results
Participant Flow
| Recruitment Details | First patient enrolled: 13 October 2008 Last patient enrolled: 7 December 2009 This study was conducted at Division of oncology, Department of Medicine of general hospitals in Korea. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Vandetanib | Placebo |
|---|---|---|
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo |
| Period Title: Overall Study | ||
| STARTED | 75 | 42 |
| COMPLETED | 75 | 42 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Vandetanib | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo | Total of all reporting groups |
| Overall Participants | 75 | 42 | 117 |
| Age, Customized (year) [Median (Full Range) ] | |||
| Median (min-Max Range) |
61
|
60.5
|
61
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
28
37.3%
|
14
33.3%
|
42
35.9%
|
| Male |
47
62.7%
|
28
66.7%
|
75
64.1%
|
| Smoking history (Number) [Number] | |||
| Smoker |
47
62.7%
|
28
66.7%
|
75
64.1%
|
| Non-smoker |
28
37.3%
|
14
33.3%
|
42
35.9%
|
| Overall response at screening (Number) [Number] | |||
| Partial Response (PR) |
44
58.7%
|
30
71.4%
|
74
63.2%
|
| Stable Disease (SD) |
31
41.3%
|
12
28.6%
|
43
36.8%
|
| WHO Performance status (Number) [Number] | |||
| 0 |
20
26.7%
|
10
23.8%
|
30
25.6%
|
| 1 |
55
73.3%
|
32
76.2%
|
87
74.4%
|
| Histology (Number) [Number] | |||
| Adenocarcinoma |
56
74.7%
|
31
73.8%
|
87
74.4%
|
| Squamous cell carcinoma |
11
14.7%
|
9
21.4%
|
20
17.1%
|
| Other |
8
10.7%
|
2
4.8%
|
10
8.5%
|
| Classification of lung tumor stage (Number) [Number] | |||
| Stage IIIb |
15
20%
|
12
28.6%
|
27
23.1%
|
| Stage IV |
60
80%
|
30
71.4%
|
90
76.9%
|
Outcome Measures
| Title | Progression-free Survival (PFS) Rate at 3 Months |
|---|---|
| Description | Progression-free survival (PFS) rate at 3 months is defined as the number of patients without evidence of progression or death after 3 months from randomisation among the PFS-evaluable patients. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The reported number of participants analyzed (Vandetanib: 63, Placebo: 38) are for PFS evaluable patient set. |
| Arm/Group Title | Vandetanib | Placebo |
|---|---|---|
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo |
| Measure Participants | 63 | 38 |
| Number [Participants] |
28
37.3%
|
12
28.6%
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | Progression-free survival (PFS) defined as the median time from randomization to death from any cause or first observed disease progression. |
| Time Frame | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Vandetanib | Placebo |
|---|---|---|
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo |
| Measure Participants | 75 | 42 |
| Median (95% Confidence Interval) [months] |
2.7
|
1.7
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Overall survival (OS) defined as the median time from randomization to death from any cause. |
| Time Frame | Every 12 weeks unless the patient withdraws consent |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Vandetanib | Placebo |
|---|---|---|
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo |
| Measure Participants | 75 | 42 |
| Median (95% Confidence Interval) [months] |
15.6
|
20.8
|
| Title | Disease of Response (DOR) |
|---|---|
| Description | Number of patients showing Complete Response (CR), Partial Response (PR) or Stable Disease (SD) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions), Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) or Stable Disease (SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum longest diameter since the treatment started) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response |
| Time Frame | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Vandetanib | Placebo |
|---|---|---|
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo |
| Measure Participants | 75 | 42 |
| Number [Participants] |
33
44%
|
17
40.5%
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | Number of patients showing Complete Response (CR) or Partial Response (PR) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response. |
| Time Frame | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Vandetanib | Placebo |
|---|---|---|
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo |
| Measure Participants | 75 | 42 |
| Number [Participants] |
14
18.7%
|
1
2.4%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Vandetanib | Placebo | ||
| Arm/Group Description | Vandetanib 300 mg, orally, once daily | Matching Placebo | ||
All Cause Mortality |
||||
| Vandetanib | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Vandetanib | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/75 (24%) | 4/42 (9.5%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 2/75 (2.7%) | 1/42 (2.4%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 3/75 (4%) | 0/42 (0%) | ||
| Dysphagia | 0/75 (0%) | 1/42 (2.4%) | ||
| Enterocolitis | 0/75 (0%) | 1/42 (2.4%) | ||
| Chest discomfort | 2/75 (2.7%) | 0/42 (0%) | ||
| Infections and infestations | ||||
| Pneumonia | 12/75 (16%) | 1/42 (2.4%) | ||
| Sepsis | 1/75 (1.3%) | 0/42 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Muscular weakness | 1/75 (1.3%) | 0/42 (0%) | ||
| Nervous system disorders | ||||
| Transient ischemic attack | 3/75 (4%) | 0/42 (0%) | ||
| Headache | 2/75 (2.7%) | 0/42 (0%) | ||
| Memory impairment | 2/75 (2.7%) | 0/42 (0%) | ||
| Convulsion | 1/75 (1.3%) | 0/42 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Productive cough | 2/75 (2.7%) | 0/42 (0%) | ||
| Cough | 2/75 (2.7%) | 0/42 (0%) | ||
| Dyspnoea | 4/75 (5.3%) | 0/42 (0%) | ||
| Pneumonitis | 1/75 (1.3%) | 0/42 (0%) | ||
| pneumothorax | 2/75 (2.7%) | 0/42 (0%) | ||
| Ileal perforation | 1/75 (1.3%) | 0/42 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 3/75 (4%) | 0/42 (0%) | ||
| Vascular disorders | ||||
| Hypertension | 2/75 (2.7%) | 0/42 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Vandetanib | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 72/75 (96%) | 37/42 (88.1%) | ||
| Eye disorders | ||||
| Vision blurred | 4/75 (5.3%) | 0/42 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 45/75 (60%) | 4/42 (9.5%) | ||
| Nausea | 13/75 (17.3%) | 6/42 (14.3%) | ||
| Constipation | 8/75 (10.7%) | 2/42 (4.8%) | ||
| Dry Mouth | 4/75 (5.3%) | 0/42 (0%) | ||
| Stomatitis | 8/75 (10.7%) | 1/42 (2.4%) | ||
| Vomiting | 6/75 (8%) | 1/42 (2.4%) | ||
| General disorders | ||||
| Asthenia | 9/75 (12%) | 3/42 (7.1%) | ||
| Chest Discomfort | 7/75 (9.3%) | 2/42 (4.8%) | ||
| Chest Pain | 12/75 (16%) | 5/42 (11.9%) | ||
| Fatigue | 5/75 (6.7%) | 3/42 (7.1%) | ||
| Mucosal Inflammation | 7/75 (9.3%) | 0/42 (0%) | ||
| Pyrexia | 5/75 (6.7%) | 2/42 (4.8%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 0/75 (0%) | 5/42 (11.9%) | ||
| Infections and infestations | ||||
| Paronychia | 4/75 (5.3%) | 0/42 (0%) | ||
| Pneumonia | 9/75 (12%) | 3/42 (7.1%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 29/75 (38.7%) | 7/42 (16.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back Pain | 5/75 (6.7%) | 4/42 (9.5%) | ||
| Musculoskeletal Chest Pain | 1/75 (1.3%) | 3/42 (7.1%) | ||
| Musculoskeletal Pain | 3/75 (4%) | 5/42 (11.9%) | ||
| Pain in Extremity | 1/75 (1.3%) | 4/42 (9.5%) | ||
| Nervous system disorders | ||||
| Dizziness | 4/75 (5.3%) | 3/42 (7.1%) | ||
| Headache | 8/75 (10.7%) | 3/42 (7.1%) | ||
| Peripheral Sensory Neuropathy | 2/75 (2.7%) | 4/42 (9.5%) | ||
| Anxiety | 5/75 (6.7%) | 1/42 (2.4%) | ||
| Psychiatric disorders | ||||
| Insomnia | 14/75 (18.7%) | 2/42 (4.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 38/75 (50.7%) | 23/42 (54.8%) | ||
| Dyspnoea | 19/75 (25.3%) | 5/42 (11.9%) | ||
| Productive cough | 29/75 (38.7%) | 15/42 (35.7%) | ||
| Dysphonia | 8/75 (10.7%) | 1/42 (2.4%) | ||
| Dyspnoea Exertional | 7/75 (9.3%) | 0/42 (0%) | ||
| Haemoptysis | 5/75 (6.7%) | 0/42 (0%) | ||
| Pharyngolaryngeal Pain | 8/75 (10.7%) | 2/42 (4.8%) | ||
| Rhinorrhoea | 3/75 (4%) | 5/42 (11.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 23/75 (30.7%) | 7/42 (16.7%) | ||
| Acne | 9/75 (12%) | 0/42 (0%) | ||
| Dry Skin | 10/75 (13.3%) | 0/42 (0%) | ||
| Hyperhidrosis | 4/75 (5.3%) | 0/42 (0%) | ||
| Rash | 58/75 (77.3%) | 11/42 (26.2%) | ||
| Skin Lesion | 8/75 (10.7%) | 3/42 (7.1%) | ||
| Vascular disorders | ||||
| Flushing | 6/75 (8%) | 0/42 (0%) | ||
| Hypertension | 13/75 (17.3%) | 0/42 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | |
| Contact-US@sanofi.com |
- D4200C00077